Clinical Pearls & Morning Reports
Shipley et al. conducted a randomized trial in men with localized prostate cancer who had been treated with radical prostatectomy, and who were to receive salvage radiation therapy for a subsequent biochemical recurrence, to evaluate whether the addition of antiandrogen therapy for 24 months during and after salvage radiation therapy could prolong overall survival, as compared with radiation therapy plus placebo. A new Review Article explains.
Q: How effective is salvage radiation therapy for biochemical recurrence of prostate cancer after radical prostatectomy for localized disease?
A: Patients with localized prostatic cancer are often treated with radical prostatectomy. More than 30% of such patients will subsequently have recurrence. This recurrence manifests first as a rising serum level of prostate-specific antigen (PSA), termed biochemical recurrence. Large, retrospective studies suggest that salvage radiation therapy after biochemical recurrence may be associated with long-term freedom from cancer recurrence. However, 50% of the patients who are treated with salvage radiation therapy will have further disease progression, particularly when there are aggressive disease features.
Q: What is bicalutamide?
A: In randomized trials, the oral agent bicalutamide, an androgen-receptor blocker, at a dose of 150 mg daily has been shown to be effective against prostate cancer. Now, 20 years after the trial by Shipley et al. was designed, gonadotropin-releasing hormone (GnRH) agonists have superseded bicalutamide as the first-choice hormonal therapy with radiation therapy, and bicalutamide at the 150-mg dose level is not approved for this purpose.
A: The randomized trial by Shipley et al. showed that the addition of 24 months of bicalutamide to salvage radiation therapy resulted in higher rates of overall survival and other important end points among surgery-treated patients with persistent or recurrent disease that was detected only because of an abnormal PSA level. Because of the relatively slow nature of prostate-cancer progression, a median follow-up of more than a decade was necessary to observe this benefit. The 12-year overall survival benefit with antiandrogen therapy was accompanied by significantly lower rates of disease-specific death, distant metastases, and second biochemical recurrence. These gains were achieved without the exacerbation of early or late bladder, bowel, hematologic, or hepatic effects, for which the rates were low in the two groups.
A: Randomized trials involving patients with nonmetastatic disease have shown that high-dose bicalutamide and GnRH agonists have similar systemic anticancer efficacy. The fully enrolled RADICALS-HD (Radiotherapy and Androgen Deprivation in Combination after Local Surgery) trial in the United Kingdom and the GETUG-16 (Group d’Étude des Tumeurs Urogénitales 16) trial in France are examining the role of contemporary androgen-deprivation therapy in the context of salvage radiation therapy, and these two trials may provide additional insights as these data mature.